scholarly journals Liver function tests and fibrosis scores in a rural population in Africa: estimation of the burden of disease and associated risk factors

Author(s):  
Geraldine A O’Hara ◽  
Jolynne Mokaya ◽  
Jeffrey P Hau ◽  
Louise O Downs ◽  
Anna L McNaughton ◽  
...  

ABSTRACTIntroductionLiver disease is a major cause of morbidity and mortality in sub-Saharan Africa. However, its prevalence, distribution and aetiology have not been well characterised. We examined liver function tests (LFTs) and calculated liver fibrosis scores in a rural population in Uganda.MethodologyA cross-sectional survey of LFTs was undertaken in 2011 in a rural population cohort in South-Western Uganda. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (AST to Platelet Ratio Index, fibrosis-4, GGT to platelet ratio, red cell distribution width to platelet ratio, and S-index) to evaluate the potential prevalence of liver disease. We collected information about alcohol intake, and infection with HIV, HBV and HCV, to determine the contribution made by these factors to liver inflammation or fibrosis.ResultsData were available for 8,099 participants (median age 30 years; 56% female). The prevalence of HBV, HCV and HIV infection were 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared to the African reference range (e.g. for AST 13% vs 3%, respectively). The prevalence of AST/ALT ratio >2 was 11%, suggestive of alcoholic hepatitis. The highest prevalence of fibrosis was suggested by the GPR score, with 24% of the population falling above the threshold for fibrosis. By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, infection with HIV or HBV, and alcohol consumption. Based on population attributable risk, the highest proportion of elevated fibrosis scores was associated with alcohol use (e.g. 64% of elevated S-index scores).ConclusionFurther work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores, and to determine aetiology of liver disease.KEY FINDINGSWhat is already known?Liver disease is not well characterised in many parts of sSA despite the high prevalence of chronic viral infections (HIV, HBV and HCV), and potential exposure to hepatotoxins including alcohol, aflatoxins and traditional herbal medicine.Non-invasive blood tests for markers of fibrosis are relatively simple and offer a safe route to assess for liver fibrosis, however, their diagnostic accuracy is not well established in sSA.Appropriate reference ranges for LFTs are crucial for optimising the sensitivity and specificity of the detection of underlying liver disease.What are the new findings?There is a disparity in the prevalence of abnormal LFTs in our study cohort when comparing two references ranges (American vs. local reference ranges).Based on GPR score, there is a high prevalence of liver fibrosis (almost 1 in 4 of this population) and elevated GPR score is associated with older age, male sex, being under-weight, infection with HIV or HBV, and alcohol consumption.Alcohol consumption accounted for 64% of abnormal S-index scores, 32% of elevated FIB-4 scores, and 19% of GPR abnormalities.What do the new findings imply?Appropriate reference ranges for LFTs are necessary to contribute to an understanding of the burden and aetiology of liver disease.Alcohol, HIV and HBV are risk factors for deranged LFTs and liver fibrosis, with alcohol making the most significant and striking contribution.Further investigation is needed to determine other factors that contribute to liver disease in this setting.

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e032890 ◽  
Author(s):  
Geraldine O'Hara ◽  
Jolynne Mokaya ◽  
Jeffrey P Hau ◽  
Louise O Downs ◽  
Anna L McNaughton ◽  
...  

ObjectivesLiver disease is a major cause of morbidity and mortality in sub-Saharan Africa, but its prevalence, distribution and aetiology have not been well characterised. We therefore set out to examine liver function tests (LFTs) and liver fibrosis scores in a rural African population.DesignWe undertook a cross-sectional survey of LFTs. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), fibrosis-4, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), red cell distribution width to platelet ratio and S-index). We collected information about alcohol intake, and infection with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV).SettingWe studied a population cohort in South-Western Uganda.ParticipantsData were available for 8099 adults (median age 30 years; 56% female).ResultsThe prevalence of HBV, HCV and HIV infection was 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared with the African reference range (eg, for AST 13% vs 3%, respectively). Elevated AST/ALT ratio was significantly associated with self-reported alcohol consumption (p<0.001), and the overall prevalence of AST/ALT ratio >2 was 11% (suggesting alcoholic hepatitis). The highest prevalence of fibrosis was predicted by the GPR score, with 24% of the population falling above the threshold for fibrosis. There was an association between the presence of HIV or HBV and raised GPR (p=0.005) and S-index (p<0.001). By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, HIV or HBV infection and alcohol consumption.ConclusionsFurther work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores and to determine the aetiology of liver disease.


2021 ◽  
Vol 15 (7) ◽  
pp. 1936-1939
Author(s):  
Shahla Mohammed Saeed Rasul ◽  
Ali Khalaf Salim ◽  
Hiwa Abubakr Hussein

Background: Nowadays, generating shear waves and simulation of the liver tissue is done using point shear-wave elastographic (pSWE) techniques which uess acoustic radiation force impulse (ARFI). Objective: This study aimed to evaluate the correlation between pSWE and liver function tests (LFTs) to predict liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Materials and methods: It was a cross sectional study conducted in an Ultrasound Clinic in Suleymaniya city. The duration of the study was from 1st of November, 2018 to 30th of June, 2019 which conducted on 50 NAFLD patients. After confirming NAFLD diagnosis, the patients were referred to Ultrasound Clinic to go under pSWE test. Results: The data showed that the mean PSWE of NAFLD patient was 4.12±0.87 Kpa; and 18% of them had high PSWE (> 4.6). Elastography fibrosis score was distributed to F0 (82%), F1 (6%), F2 (8%) and F3 (4%). There was a significant association between high APRI and high Aspartate Aminotransferase/Alanine Aminotransferase(AST/ALT) ratio (p=0.04). There was also a highly significant association between elastography fibrosis score and APRI fibrosis score among NAFLD patients (p<0.001). Conclusion: This study showed that the pSWE is a valuable noninvasive diagnostic technique for predicting liver fibrosis among NAFLD patients and there is significant correlation between APRI and pSWE scores. Keywords: Non-alcoholic fatty liver disease, Point shears wave elastography, Liver fibrosis.


2015 ◽  
Vol 38 (2) ◽  
Author(s):  
Arnold von Eckardstein

AbstractOwing to the high prevalence and associated complications of liver fibrosis, of any etiology, and nonalcoholic fatty liver disease (NAFLD), both have become important public health issues. Liver biopsy is considered the gold standard for diagnosis and staging of liver fibrosis, as well as NAFLD. Recent studies have discovered and validated several non-invasive biochemical biomarkers and imaging procedures for the diagnostics of liver fibrosis and NAFLD. In comparison to patented tests (FibroTest


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Brenda Nherera ◽  
Kudakwashe Mhandire ◽  
Tinashe K. Nyazika ◽  
Alfred Makura ◽  
Cuthbert Musarurwa ◽  
...  

Background: The prevalence of morbidity and mortality associated with liver disease among HIV-infected individuals on combination antiretroviral therapy (ART) is high. Early screening of liver disease is essential, as it provides an opportunity for successful treatment. Hence, there is a need for reliable, inexpensive and non-invasive early markers of hepatic damage.Objectives: Non-invasive algorithms are available for assessing the extent of liver fibrosis as markers of ongoing inflammatory damage. This study compared the use of the FibroTest, Fibrosis-4 (FIB-4) index, APRI test and AST:ALT ratio in assessing liver fibrosis in combination ART-experienced individuals.Methods: In a comparative cross-sectional study, 79 participants between the ages of 8 and 62 years were recruited. The performance of each fibrosis algorithm was determined using established cut-off scores for clinically significant liver fibrosis.Results: The prevalence of liver fibrosis as determined by the FibroTest, FIB-4 index, APRI test and AST: ALT ratio were 19.0%, 21.5%, 12.7% and 79.7%, respectively. For individual biomarkers, A-2M concentration (p < 0.001) and AST activity (p = 0.003) remained significantly elevated in participants with fibrosis than those without as defined by FibroTest and APRI test, respectively, after adjustments for multiple comparisons.Conclusion: Our data demonstrate a high prevalence of asymptomatic liver fibrosis among combination ART-experienced individuals in Zimbabwe, and this warrants adequate monitoring of liver fibrosis in individuals on ART. Discordance of fibrosis results among the algorithms and individual biomarkers and calls for further work in identifying optimal biomarkers for detection of asymptomatic fibrosis.Keywords: Liver fibrosis; Non-invasive methods; Biomarkers; Combination anti-retroviral therapy; Zimbabwe.


2018 ◽  
Vol 16 (7) ◽  
pp. 1138-1145.e5 ◽  
Author(s):  
Llorenç Caballería ◽  
Guillem Pera ◽  
Ingrid Arteaga ◽  
Lluís Rodríguez ◽  
Alba Alumà ◽  
...  

2011 ◽  
Vol 300 (4) ◽  
pp. G516-G525 ◽  
Author(s):  
Bin Gao ◽  
Ekihiro Seki ◽  
David A. Brenner ◽  
Scott Friedman ◽  
Jessica I. Cohen ◽  
...  

Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, whereas activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol-mediated acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease.


2021 ◽  
Vol 15 (6) ◽  
pp. 1990-1994
Author(s):  
Shahla Mohammed Saeed Rasul ◽  
Ali Khalaf Salim ◽  
Hiwa Abubakr Hussein

Aim: of this study is to correlate between point shear wave elastography(pSWE) and liver function tests (LFTs) to predict liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Materials and methods: this study is a cross sectional study conducted in Ultrasound Clinic in Suleymaniya city. The duration of the study was through the period from 1st of November, 2018 to 30th of June, 2019 on 50 NAFLD patients. After confirming NAFLD diagnosis, the patients were referred to Ultrasound Clinic to complete Point Shear Wave Elastography (PSWE). Results: showed a mean PSWE of NAFLD patient was 4.12±0.87 Kpa; 18% of them had high PSWE (> 4.6). Elastography fibrosis score was distributed to F0 (82%), F1 (6%), F2 (8%) and F3 (4%). The Aspartate Aminotransferase Platelet Ratio Index (APRI) fibrosis scores were distributed to F0 (48%), F1-3 (48%) and F4 (4%), There was a highly significant association between elastography fibrosis score and APRI fibrosis score of NAFLD patients (p<0.001), There was no significant association between elastography fibrosis score and Aspartate Aminotransferase/Alanine Aminotransferase (AST/ALT) values of NAFLD patients (p=0.5). Conclusion: this study showed that the point shear wave elastography is a valuable noninvasive diagnostic technique for predicting significant liver fibrosis among patients with non-alcoholic liver fatty diseases and there is significant correlation between APRI score and pSWE score. The current gold standard in the diagnosis and staging of liver fibrosis is liver biopsy. Point shear wave elastography is among the noninvasive procedures to assess liver fibrosis. Keywords: Non-alcoholic fatty liver disease, Point shears wave elastography, Liver fibrosis.


2018 ◽  
Author(s):  
Hannah L Paish ◽  
Lee H Reed ◽  
Helen Brown ◽  
Mark C Bryan ◽  
Olivier Govaere ◽  
...  

Summary boxWhat is already known about this subject?Currently there are no effective anti-fibrotic drugs to treat liver fibrosis and there is an urgent unmet need to increase our knowledge of the disease process and develop better tools for anti-fibrotic drug discovery.Preclinical in vitro cell cultures and animal models are widely used to study liver fibrosis and test anti-fibrotic drugs, but have shortfalls; cell culture models lack the relevant complex cell-cell interactions of the liver and animal models only reproduce some features of human disease.Precision Cut Liver Slices (PCLS) are structurally representative of the liver and can be used to model liver fibrosis and test anti-fibrotic drugs. However, PCLS are typically cultured in elevated, non-physiological oxygen levels and only have a healthy lifespan of 48h.What are the new findings?We have developed a novel bioreactor culture system that increases the longevity of functional PCLS to up to 6 days under normoxic conditions.Bioreactor cultured PCLS can be used to model fibrogenesis in both normal and fibrotic PCLS using a combination of biochemical and histological outputs.Administration of an Alk5 inhibitor effectively limits fibrogenesis in normal rodent and human PCLS and in rodent PCLS with established fibrosis.How might it impact on clinical practice in the foreseeable future?The extended longevity of bioreactor cultured PCLS represent a novel pre-clinical tool to investigate the cellular and molecular mechanisms of liver fibrosis.Bioreactor cultured human PCLS offer a clinically relevant system to test efficacy of anti-fibrotic drugs.AbstractObjectivePrecision cut liver slices (PCLS) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two-dimensional mono or co-cultures. The objective of this study was to develop a bioreactor system to increase the healthy lifespan of PCLS and model fibrogenesis.DesignPCLS were generated from normal rat or human liver, or 4-week carbon tetrachloride-fibrotic rat liver and cultured in our patented bioreactor. PCLS function was quantified by albumin ELISA. Fibrosis was induced in PCLS by TGFβ1 and PDGFββ stimulation. Alk5 inhibitor therapy was used. Fibrosis was assessed by fibrogenic gene expression, Picrosirius Red and αSmooth Muscle Actin staining, hydroxyproline assay and collagen 1a1, fibronectin and hyaluronic acid ELISA.ResultsBioreactor cultured PCLS are viable, maintaining tissue structure and stable albumin secretion for up to 6 days under normoxic culture conditions. Conversely, standard static transwell cultured PCLS rapidly deteriorate and albumin secretion is significantly impaired by 48 hours. TGFβ1 and PDGFββ stimulation of rat or human PCLS induced fibrogenic gene expression, release of extracellular matrix proteins, activation of hepatic myofibroblasts and histological fibrosis. Fibrogenesis slowly progresses over 6-days in cultured fibrotic rat PCLS without exogenous challenge. Alk5 inhibitor limited fibrogenesis in both TGFβ1 and PDGFββ stimulated PCLS and fibrotic PCLS.ConclusionWe describe a new bioreactor technology which maintains functional PCLS cultures for 6 days. Bioreactor cultured PCLS can be successfully used to model fibrogenesis and demonstrate efficacy of an anti-fibrotic therapy.


Sign in / Sign up

Export Citation Format

Share Document